Metabolomic Deficiencies Characteristic of Chronic Fatigue Syndrome

Mitochondrial metabolism is one of the pathways affected in chronic fatigue syndrome.

In a study designed to test the utility of targeted metabolomics in the diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), researchers identified a unique chemical signature that differentiates affected patients from healthy individuals.

The study, led by Dr Robert K. Naviaux, MD, PhD of The Mitochondrial and Metabolic Disease Center at the University of California’s San Diego School of Medicine, was published August 29 in the Proceedings of the National Academy of Sciences in the United States .1

Ronald W. Davis, PhD, director of Stanford Chronic Fatigue Syndrome Research Center of Stanford University School of Medicine commented on the findings of Dr Naviaux’s group on the the Open Medicine Foundation website, where he serves as director of the Scientific Advisory Board.

“It is the most important and groundbreaking study of ME/CFS to date. Extending recent indications of metabolic alterations in ME/CFS, this study provides the first comprehensive, quantitative demonstration of the metabolomic deficiencies that characterize the disease.”

Metabolomics is, according to a white paper by leaders in the field, “the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids.”2 These biochemicals represent the end-product of cellular processes.

For their study, Dr Naviaux and colleagues measured 612 plasma metabolites in 45 patients who met the diagnostic criteria for ME/CFS, and in 39 age- and sex-matched normal controls.

Results showed that patients with ME/CFS had aberrations in 20 out of 63 identified metabolic pathways, and that 80% of their diagnostic metabolites were lowered, suggesting the presence of a hypometabolic syndrome.

Dr Naviaux and colleagues found that the metabolic signature of CFS was similar to that of dauer, an adaptive state found in certain nematodes. In dauer, environmental insults trigger changes in mitochondrial functions, fuel preferences, behavior, and physical features. These alterations allow the organism to survive harsh conditions, but at the cost of diminished functional capacity.

While the research team has no plans to develop a diagnostic assay based on their results, study co-author Dr Eric Gordon noted that better diagnostics potentially have an important role to play in how patients with CFS are perceived.

Dr Gordon is a physician whose practice focuses on complex chronic illnesses, many of whom have diagnostic tests. “In the absence of a clear cut diagnostic test, people with CFS are often ridiculed and treated as if they’re malingering – or if people are being kind about it, they’ll treat them as depressed,” he told Clinical Pain Advisor.

A 2011 study published in the Lancet – the PACE trial – was criticized by patient advocacy groups for its endorsement of cognitive behavioral therapy and graded exercise therapy as primary components of treatment.3,4

“The idea that a psychosocial model of treatment is more appropriate in CFS than in any other disease is incorrect,” Dr Gordon said. “All chronic diseases do better with a psychosocial component to their treatment. Illness will exacerbate all of our underlying neurotic tendencies. This is the human response to illness.”

Summary and Clinical Applicability

“Only about 25% of the metabolite disturbances found in each person were needed for the diagnosis of CFS,” the investigators wrote in the paper’s conclusion.

“About 75% of the metabolite abnormalities were unique to the individual and useful in guiding personalized treatment. The study of larger cohorts from diverse geographical areas, and comparison with related medical disorders like depression and posttraumatic stress disorder, will be needed to validate the universality and specificity of these findings. The finding of an objective chemical signature in CFS helps to remove diagnostic uncertainty, will help clinicians monitor individualized responses to treatment, and will facilitate multicenter clinical trials.”

Goldin R. PACE: The research that sparked a patient rebellion and challenged medicine. STATS.org. http://www.stats.org/pace-research-sparked-patient-rebellion-challenged-medicine/. Published March 21, 2016. Accessed September 26, 2016.